Age-Dependent Differences in the Antiviral Response of the Respiratory Epithelium

Age is an established risk factor for severe viral respiratory infections, yet the mechanisms driving increased severity of illness in infants and older adults remain incompletely understood. The respiratory epithelium is the primary target of viral infection and how it orchestrates the immune response may be a key determinant of clinical outcomes. The profound age-related difference in susceptibility to severe Coronavirus disease 2019 (COVID-19) brought increased attention to the epithelial response to viral infection in children and adults, adding significant data to the preexisting body of work largely focused on influenza and respiratory syncytial virus (RSV). This review synthesizes current knowledge on the structural and functional differences in the respiratory epithelium between children and adults at baseline and during viral infection. We review the variable and heterogenous human studies in addition to in vitro and animal model data to identify key gaps in current knowledge. Here, we advocate for a more complete understanding of age-dependent differences in the respiratory epithelial response to viral infection to uncover therapeutic targets for prevention and treatment of viral-associated respiratory failure.